CD8⁺ T cells in healthy aging: Mechanisms, neuro-immune crosstalk, and functional remodeling

Aging profoundly reshapes immune function, leading to alterations in T cell homeostasis, differentiation, and responsiveness. Among the most affected populations are CD8⁺ T cells, which play pivotal roles in host defense, tissue surveillance, and immunoregulation. Despite extensive research on immunosenescence, the molecular and systemic mechanisms governing CD8⁺ T cell function during healthy aging remain poorly defined. This Research Topic aims to gather high-quality contributions that elucidate how endogenous and environmental factors shape CD8⁺ T cell biology across the lifespan, with particular emphasis on maintaining immune resilience and neuro-immune homeostasis in aging.

We encourage submissions of original research articles, reviews, perspectives, and methodological advances that address the fundamental and translational aspects of CD8⁺ T cell biology relevant to aging. In keeping with the scope of the T Cell Biology section, we are particularly interested in studies that dissect molecular signaling, receptor-ligand interactions, transcriptional programs, and intercellular communication pathways that regulate CD8⁺ T cell activation, proliferation, differentiation, and effector or regulatory functions. Investigations employing multi-omics, immunomics, and structural or biochemical approaches to unravel these mechanisms are especially welcome.

Emerging evidence highlights the existence of a dynamic neuro-immune crosstalk, where CD8⁺ T cells contribute to brain function, homeostasis, and neuroprotection—or, conversely, to neuroinflammation. Aging-associated changes in cytokines, hormones, neurotransmitters, and tissue-derived factors profoundly influence CD8⁺ T cell phenotypes and their capacity to respond to systemic and local challenges. Understanding these interactions is key to identifying strategies that preserve healthy immune and neurological function in later life.

We invite submissions that explore, but are not limited to:

-Endogenous and environmental factors (e.g., cytokines, hormones, metabolic signals, neurotransmitters) regulating CD8⁺ T cell differentiation, metabolism, and survival during aging.
-Systemic and tissue-level remodeling of CD8⁺ T cell immunity in the context of neuro-immune communication and central nervous system (CNS) homeostasis.
-Age-dependent changes in effector-memory CD8⁺ T cells and their contributions to chronic and neurodegenerative diseases.
-Computational and single-cell multi-omics approaches for decoding CD8⁺ T cell heterogeneity and function in large human or translational datasets.
-Therapeutic or immunomodulatory strategies aimed at mitigating harmful effects or enhancing protective roles of CD8⁺ T cells to promote healthy aging.

By integrating insights from molecular immunology, neurobiology, and systems biology, this Research Topic seeks to advance our understanding of how CD8⁺ T cell regulation supports health across the lifespan. In line with the T Cell Biology section’s mission and the United Nations Sustainable Development Goal 3 (Good Health and Well-being), this collection will foster interdisciplinary dialogue and highlight mechanisms that sustain immune competence and tissue integrity during aging.

Sandros Da Mesquita is listed as an inventor in patent applications concerning modulating lymphatic vessels in neurological disease (University of Virginia Licensing and Ventures Group; and PureTech Ventures). All other topic editors declare no conflict of interest

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Policy and Practice Reviews
• Review
• Study Protocol
• Systematic Review
• Technology and Code

Keywords: CD8⁺ T cells, Effector-memory, Effector memory, CD45RA, Neuroimmune cross-talk, Age-related disease, Neurodegeneration, Bioinformatics, Transcriptomics, Epigenomics

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.